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. Author manuscript; available in PMC: 2021 Apr 15.
Published in final edited form as: Biol Psychiatry. 2020 Feb 13;89(8):745–756. doi: 10.1016/j.biopsych.2020.02.001

Table 2.

BACE1 Substrates and Their Physiological Roles

BACE1 Substrate Physiological Role
APP Regulates neurite outgrowth, synapse formation, and synaptic plasticity; also regulates metal homeostasis
APLP1 Regulates neurotransmission and plasticity in CNS synapses
APLP2 Regulates synaptic function and plasticity in CNS
Contactin 2 Regulates axon guidance, cell adhesion, and neurite outgrowth
Jagged 1 Balances astrogenesis and neurogenesis; notch signaling influences neural plasticity, long-term memory, and synapse remodeling transmitter release through astrocytes
CHL1 Regulates axon guidance, cell adhesion, neuronal migration, and neurite outgrowth
Neurexin 1α and 3β Regulates synapse assembly and maintenance
NRG1 Regulates myelination, neuronal migration, and oligodendrocyte differentiation; also regulates synaptic transmission and plasticity via neurotransmitter receptors
SEZ6 Regulates dendritic arborization and affects excitatory synapse development and maintenance and formation of neuronal circuits
SEZ6L Regulates synapse maturation, tumor suppressor function, and free cholesterol levels
β (β1–4) Auxiliary Subunits of the VGSC Subtype Nav1 Modulates cell surface expression of Nav1 sodium channels and thus controls excitability and propagation of action potentials in the neuronal membrane
VGSC Accessory Subunits KCNE1 and KCNE2 Regulates cardiac and brain potassium channel subunit trafficking and maintenance of membrane excitability

APLP1/2, amyloid-like protein 1/2; APP, amyloid precursor protein; CHL1, neural cell adhesion molecule L1; CNS, central nervous system; NRG1, neuregulin 1; SEZ6, seizure-related protein 6; SEZ6L, seizure-related protein 6 precursor protein; VEGFR1, vascular endothelial growth factor receptor 1; VGSC, voltage-gated sodium channels. [Adapted with permission from Das and Yan (144).]